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AbstractReconstructing transmission pathways and defining the underlying determinants of virus diversity is critical for developing effective control measures. Whole genome consensus sequences represent the dominant virus subtype which does not provide sufficient information to resolve transmission events for rapidly spreading viruses with overlapping generations. We explored whether the within-host diversity of respiratory syncytial virus quantified from deep sequence data provides additional resolution to inform on who acquires infection from whom based on shared minor variants in samples that comprised epidemiological clusters and that shared similar genetic background. We report that RSV-A infections are characterized by low frequency diversity that occurs across the genome. Shared minor variant patterns alone, were insufficient to elucidate transmission chains within household members. However, they provided inference on potential transmission links where phylogenetic methods were uninformative of transmission when consensus sequences were identical. Interpretation of minor variant patterns was tractable only for small household outbreaks.

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